Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein

Authors

  • Felicia Grasso,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
    • F.G. and D.R.M.N. contributed equally to this work

  • Donatella R.M. Negri,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
    • F.G. and D.R.M.N. contributed equally to this work

  • Stefania Mochi,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Alessandra Rossi,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Armando Cesolini,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Andrea Giovannelli,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Maria Vincenza Chiantore,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Pasqualina Leone,

    1. Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Colomba Giorgi,

    1. Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy
    Search for more papers by this author
  • Andrea Cara

    Corresponding author
    1. Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy
    • Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy
    Search for more papers by this author
    • Tel.: +39-6-4990-3503; Fax: +39-6-4938-7199


Abstract

Persistent infection with high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer, one of most common cancer among woman worldwide, and represents an important risk factor associated with other anogenital and oropharyngeal cancers in men and women. Here, we designed a therapeutic vaccine based on integrase defective lentiviral vector (IDLV) to deliver a mutated nononcogenic form of HPV16 E7 protein, considered as a tumor specific antigen for immunotherapy of HPV-associated cervical cancer, fused to calreticulin (CRT), a protein able to enhance major histocompatibility complex class I antigen presentation (IDLV-CRT/E7). Vaccination with IDLV-CRT/E7 induced a potent and persistent E7-specific T cell response up to 1 year after a single immunization. Importantly, a single immunization with IDLV-CRT/E7 was able to prevent growth of E7-expressing TC-1 tumor cells and to eradicate established tumors in mice. The strong therapeutic effect induced by the IDLV-based vaccine in this preclinical model suggests that this strategy may be further exploited as a safe and attractive anticancer immunotherapeutic vaccine in humans.

Ancillary